Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis

University Health Network, Toronto15 enrolled

Overview

Current evidence on tapering of tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) is still hampered by heterogeneity in tapering regimens, selection and performance biases, and lack of data on optimized treatment dosing strategies especially in real-world clinical settings. This study aims to contribute to the ongoing investigation of disease-activity-guided tapering of TNFi in axSpA in the form of a prospective, randomized controlled trial.

This is a 48-week randomized, controlled, open-label, non-inferiority trial of patients with radiographic or non-radiographic axial spondyloarthritis. The study will include 156 patients with inactive disease or low disease activity (LDA) for at least 6 months on a TNFi at the time of randomization. Participants will be randomized using a 1:1 ratio to either the tapered-dose arm or the standard-dose arm of TNFi. Progressive tapering of TNFi according to a predefined protocol will be allowed as long as the patient is able to maintain inactive disease or LDA during the study period. We hypothesize that, in patients with 6 months or more of inactive or low-activity axial spondyloarthritis, tapered-dose TNFi are non-inferior to standard-dose TNFi in sustaining the disease state for at least 1 year.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Axial Spondyloarthritis

Interventions

Tapered doses of TNFiDRUG

To be given subcutaneously via a prefilled syringe/autoinjector (etanercept, adalimumab, certolizumab pegol, golimumab) or intravenously via infusion (infliximab) at increasing dose intervals as specified

Standard dose of TNFiDRUG

To be given subcutaneously via a prefilled syringe/autoinjector (etanercept, adalimumab, certolizumab pegol, golimumab) or intravenously via infusion (infliximab)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult axSpA patients satisfying the 2009 Assessment of SpondyloArthritis International Society (ASAS) Classification Criteria * Currently enrolled in the SPARCC Program with successful completion of standard data collection protocol in the Spondylitis Clinic of UHN-Toronto Western Hospital * Have sustained inactive disease or LDA with an ASDAS of \<2.1 or BASDAI \<4 for at least 6 months * On a stable dose of a TNFi (infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab) * Must not be pregnant Exclusion Criteria: * Adults axSpA patients with active extra-articular manifestations such as inflammatory bowel disease, psoriasis, and/or uveitis * Have comorbidities that may preclude clinical assessment (i.e. fibromyalgia or other chronic pain syndromes; chronic inflammatory diseases other than axSpA) * Have diagnosed psychiatric or personality disorders * Pregnant * Not enrolled in the Spondyloarthritis Research Consortium of Canada (SPARCC) Program

Locations (1)

University Health Network - Toronto Western Hospital

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

Proportion of patients able to maintain inactive disease or low disease activity, defined as Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 to 2.1 or Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) of <4 on tapered-dose TNFi

The ASDAS and BASDAI are measures of axial spondyloarthritis disease activity for the past week. The ASDAS has 5 components scored from 0 to 10 (none to very severe). The following formula is used to compute for the ASDAS: (0.121 × back pain score) +(0.058 × score for duration of morning stiffness) + (0.11 × patient global assessment score) + (0.073 × peripheral pain/swelling score) + (0.579 × log(CRP+1)). The scores range from 0 (no disease activity) to infinity (being determined by the level of CRP). The disease is considered inactive if the final score is \<1.3, and low if \<2.1. The BASDAI consists of six items, with each item being scored from 0 ("none") to 10 ("very severe"). The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity. A BASDAI of \<4 indicates inactive or low disease. As opposed to ASDAS, BASDAI does not include CRP in its formula. Either ASDAS or BASDAI is acceptable in clinical practice.

Time frame: Weeks 12, 24, 36, and 48

Secondary Outcomes

Proportion of patients experiencing a disease flare by ASDAS or BASDAI

Flare is defined in this study as either of the following: 1. loss of inactive disease or LDA (ASDAS ≥2.1 or BASDAI ≥4) - see definitions above 2. minimal clinically important worsening, defined as an increase in ASDAS by ≥0.9 on two consecutive visits

Time frame: Up to Week 48

Proportion of patients with functional limitation measured using the Bath Ankylosing Spondylitis Functional Index (BASFI)

The BASFI measures the degree of functional limitation. It is composed of a set of 10 questions relating to activities during the past week. Each item is scored from 0 ("easy") to 10 ("impossible"). The final BASFI is the mean of the 10 scores with the total score ranging from 0 to 10. Lower scores indicate better physical function.

Time frame: Up to Week 48

Data from ClinicalTrials.gov

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